High affinity, low capacity, chemically specific steroid hormone receptors composed of protein are present on low concentration in hormonally responsive cells of steroid hormone sensitive target cells. These receptors recognize steroid hormones by means of chemically specific intermolecular interaction after the hormes enter the cell. The receptors also detect the amount of hormone present by the same mechanism. The receptor-hormone complex carries the hormonal information to the cell nucleus and there modulates cellular function by means of specific interactions with prescribed segments of the genome. This description of the molecular mechanism of steroid hormone action makes clear the fact that responsiveness of the target cell to the regulatory steroid hormone is directly dependent on the properties and concentration of the receptor. In this application we propose experiments on the regulation of the specific estrogen receptor in a permanent cell line derived from rat endometrium and maintained in continuous cell culture. We have characterized the receptor physically and chemically by standard biochemical methods, and we will examine the effects of variation in the environment of the cells on the amount, biosynthesis, degradation and properties of the receptor. The results of these studies of receptor regulation will be significant in a variety of problems in the general area of reproductive biology such as implantation, uterine growth and contraception in pregnancy.